The long-term objective of this application is to be able to diagnose clinically significant immunological abnormalties in patients with systemic lupus erythematosus, rheumatoid arthritis and other rheumatic diseases from small samples of blood. This will be accomplished by quantitation and functional analysis of specific lymphocyte populations (or subsets) Special emphasi will be placed on continuing efforts to characterize L lymphocytes, a newly described major population with membrane-labile IgG determinants which comprise 10 to 20 per cent of total blood lymphocytes. These lymphocytes have unique especially avid Fc receptors. The site of origin, the specific relationship (or lack of one) with T and B cells, and their involvement in autoimmune phenomenon such as the lymphopenia of SLE and hyperactive immunoglobulin production in SLE will be investigated. Highly purifid lymphocyte populations will be prepared by previously described adherence and rosetting techniques. The interactions of L lymphocytes and immune complexes in the enhancement as well as the inhibition of antibody-dependent cytotoxic mechanisms will be explored. The modulating effects of L lymphocytes exposed to various types of immune complexes on 1) the initial proliferative response of T lymphocytes, 2) T lymphocyte cytotoxicity, 3) immunoglobulin release by B lymphocytes, 4) cytotoxic properties of activated monocytes will be investigated. These functional properties will be examined with micro or mini-micro methods. Patients with SLE and RA will be examined during various stages of disease and cell methods will be designed to distinguish between intrinsic cellular and humoral defects. Studies on the inhibitor, Lymphocyte Regulatory Gammaglobulin, will be continued. Immunological abnormalities found with these in vitro methods will be compared with disease activity and an evaluation of delayed hypersensitivity to common skin test antigens. Information gained by the approach should lead to new methods to treat patients with these diseases.